On the Regioselectivity for the Michael Addition to Unsymmetric Fumaric Derivatives

Abstract

The mechanism of regioselective Michael addition of thiols to unsymmetric fumaric derivatives was investigated. The competitive reaction between tert-butyl acrylate and ethyl acrylate indicated that ethyl acrylate underwent much faster addition by 4.4 times than tert-butyl ester. The rate difference was enhanced to 8.4 times by the presence of lithium cation. The presence of base promoted the Michael addition to acrylate ester much faster than acrylamide, while the absence of base prompted the addition to amide very much. PM3 calculation for fumaric esteramide showed C2 position, which is beta-carbon to the ester group, was activated to the nucleophilic attack. The amide group in the protonated esteramide was activated by the contribution of iminiumion intermediate, which prompted the addition to C3 carbon, the beat carbon to the amide group, exclusively.